This invention relates to compounds which are useful in alleviating depression in mammals.
The following publications disclose 5,10-iminodibenzocycloheptenes:
J. w. lown and K. Matsumoto, J. Org. Chem., 36, 1405 (1971) PA1 French Pat. No. 2,170,862 PA1 French Pat. No. 2,174,771 PA1 U.s. pat. No. 4,009,273 PA1 Z is C.sub.2 -C.sub.3 alkylene; and PA1 R.sup.1 and R.sup.2, independently, are H or C.sub.1-4 alkyl. ##STR4## where X and Y, independently, are H, F, Cl, Br, C.sub.1-4 alkyl, C.sub.1-4 alkoxy, CF.sub.3 or C.sub.1-4 alkyl sulfonyl with the proviso that one of X and Y is H; PA1 Z is C.sub.2 -C.sub.3 alkylene PA1 R.sup.1 and R.sup.2, independently, are H or C.sub.1-4 alkyl, PA1 R.sup.3 is H or C.sub.1-4 alkyl, and PA1 R.sup.4 is H or halogen.
The compounds have the structure ##STR1## wherein the nitrogen can have H, lower alkyl, hydroxyalkyl, aminoalkyl, carbamyl or carbonyl containing groups, and the 11-position can have hydrogen or oxygen. The references show no substituent on the 5-position except for phenyl shown by Lown et al. Suitable utility, if disclosed for these compounds, is as an anticonvulsant, antidepressant, sedative or stimulant.
Netherlands Pat. No. 147,935 discloses compounds as antidepressants of the formula: ##STR2## where X, X', R, R' and R" represent various substituents.
Mental illness encompasses both psychoses and neuroses. Symptoms requiring treatment include depression, anxiety, agitation, and hallucinations. Among the drugs used particularly for treatment of both reactive and endogenous depressions are monoamine oxidase (MAO) inhibitors, such as iproniazide, tranylcypromine, nialamide, phenelzinc, and pargyline, and the non-MAO-inhibiting tricyclic aromatic dibenzazepines, such as imipramine, and dibenzocycloheptenes such as amitriptyline.
All of these drugs have adverse side effects that limit their usefulness. MAO inhibitors may benefit milder forms of depression, but the risk of serious toxic effects is a strong argument against their use. They may cause liver damage and acute hypertension, especially if given in conjunction with cheese, bananas, or other amine-containing foods. The MAO inhibitors may also cause tremors, insomnia, hyperhydrosis, agitation, hypermanic behavior, confusion, hallucinations, convulsions and orthostatic hypotension. They frequently cause dizziness, vertigo, headache, inhibition of ejaculation, difficulty in urination, weakness, fatigue. dry mouth, constipation and blurred vision.
Imipramine may cause blurred vision, dryness of mouth, constipation, urinary retention, orthostatic hypotension, respiration depression, myocardial infraction, and congestive heart failure. Similar difficulties are experienced with amitriptyline.
There is a continuing need for psychotherapeutic agents that have fewer side effects than the drugs in use today; use for psychotherapeutic agents that have different modes of action than presently used agents, since none of these is completely effective.
The present invention results from efforts to develop new, safe, and effective psychotherapeutic compounds with minimal side effects.